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Viruses
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HIV Reservoir Establishment in Myeloid Cells, Restriction Mechanisms and Therapeutic...
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HIV Reservoir Establishment in Myeloid Cells, Restriction Mechanisms and Therapeutic Strategies

A Special Issue of Viruses (ISSN 1999-4915) belonging to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 25 December 2026 | Viewed by 921

Editors

Dr. Yuyang Tang

E-Mail Website
Guest Editor
1. UNC HIV Cure Center, University of North Carolina, Chapel Hill, NC 27599, USA
2. Institute of Global Health & Infectious Diseases, University of North Carolina, Chapel Hill, NC 27599, USA
Interests: HIV reservoirs; latency; HIV persistent infection in the central nerve system (CNS); HIV-associated neurocognitive disorders (HAND)
Special Issues, Collections and Topics in MDPI journals
Dr. Kiera L. Clayton

E-Mail Website
Guest Editor
Chan Medical School, University of Massachusetts, Worcester, MA, USA
Interests: HIV reservoirs; myeloid cells; immune evasion; latency reversal; NK cells

Special Issue Information

Dear Colleagues,

While resting CD4+ T cells remain the best-characterized HIV reservoir, increasing evidence highlights an important role for myeloid cells—including tissue-resident macrophages and microglia—in sustaining persistent infection across tissues. However, limited access to tissue-resident myeloid populations has restricted our understanding of their contribution to HIV persistence. Emerging studies further suggest that interactions between CD4+ T cells and myeloid cells, including viral transfer and inflammatory crosstalk, contribute to reservoir maintenance and tissue injury. In addition, host factors such as substance use, aging, sex differences, and comorbidities are increasingly recognized as important modulators of HIV reservoir size, distribution, and activity.

This Special Issue will highlight recent advances in HIV persistence within myeloid reservoirs and their interactions with T cell reservoirs in the CNS and peripheral tissues. We welcome studies addressing mechanisms of viral persistence, tissue-specific reservoir biology, inflammation-driven tissue injury, host restriction factors, the impact of substance use and comorbidities, and emerging single-cell, spatial, and translational approaches for targeting myeloid reservoirs in HIV cure strategies.

Dr. Yuyang Tang
Dr. Kiera L. Clayton
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • HIV reservoirs
  • myeloid cells
  • T cells
  • immune activation and inflammation and tissue injury

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Published Papers (1 paper)

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Review

23 pages, 1590 KB  
Review
The Rectal Mucosal Myeloid Niche in HIV-1 Persistence: Reservoir Support, Viral Sequestration, and Therapeutic Opportunities
by Hanyi Zhang, Peiming Huang, Xu Zhang and Ting Pan
Viruses 2026, 18(8), 858; https://doi.org/10.3390/v18080858 - 5 Aug 2026
Viewed by 644
Abstract
Persistent HIV-1 reservoirs remain a major barrier to a durable functional cure despite long-term suppressive antiretroviral therapy. Although resting memory CD4+ T cells constitute the best-characterized cellular reservoir, tissue microenvironments shape viral persistence and immune clearance. The rectal mucosa represents a specialized [...] Read more.
Persistent HIV-1 reservoirs remain a major barrier to a durable functional cure despite long-term suppressive antiretroviral therapy. Although resting memory CD4+ T cells constitute the best-characterized cellular reservoir, tissue microenvironments shape viral persistence and immune clearance. The rectal mucosa represents a specialized tissue niche containing HIV-susceptible target cells, antigen-presenting cells, microbial products, inflammatory cues, and local metabolic signals. Within this setting, myeloid-lineage cells, particularly tissue-resident macrophages and dendritic cells, may contribute to HIV-1 persistence through mechanisms distinct from classical T-cell latency. Here, we review how rectal mucosal macrophages may support HIV-1 persistence through longevity, resistance to apoptosis, metabolic adaptation, epigenetic regulation, and sequestration of virions within virus-containing compartments. We also discuss the dual role of mucosal dendritic cells as sentinels that capture and transfer HIV-1 to CD4+ T cells, while considering the limited evidence for inducible proviral persistence in selected anatomical and cellular contexts. Importantly, we further distinguish bona fide reservoir-bearing cells from reservoir-supportive mechanisms, including viral capture, trans-infection, immune suppression, and niche-mediated protection. We also highlight how mucosal dysbiosis, barrier disruption, microbial metabolites, chronic interferon signaling, and immunoregulatory myeloid programs may stabilize HIV-1 persistence in rectal tissues. Integrating intact proviral assays, functional measurements, single-cell profiling, multiplex imaging, and spatial transcriptomics will be critical for defining myeloid-associated persistence and guiding tissue-targeted HIV-1 cure strategies. Full article
(This article belongs to the Special Issue HIV Reservoir Establishment in Myeloid Cells, Restriction Mechanisms and Therapeutic Strategies)
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